The experiments presented in this report and proposed for the coming year are a continuation of the comprehensive investigation of problems associated with cardiac transplantation which has been continuing in this laboratory for almost two decades. The main areas of investigation are the control of the immune response in cardiac transplantation and study of the problems associated with complete heart and lung transplantation. In addition to these areas, a major goal is advanced training in cardiac transplantation immunology and physiology for postdoctoral surgical fellows. To study the control of the immune response, experiments have been performed using antiplatelet agents, total lymphoid irradiation (TLI), antithymocyte globulin, and cyclosporin A. Antiplatelet agents used in heterotopic rat cardiac transplants prolong graft survival, espeically aspirin and sodium salicylate. When these agents are combined with azathioprine they result in severe bone marrow suppression in dog heart graft recipients. Inconclusive results on graft survival have been found in monkeys treated with antiplatelet agents. Antithymocyte globulin is synergistic with TLI for prolonging cardiac graft survival in monkeys. The fungal metabolite, cyclosporin A, is an excellent immunosuppressive agent in rats and monkeys, although infectious complications increase with higher doses and rejection is not completely prevented at lower doses. Long-term survival of monkeys following orthotopic cardiac transplantation has been shown with cyclosporin A alone. Heart and lung transplantation has been performed in monkeys with extended survival of autotransplants. Allografts have been followed to the time of rejection. Pulmonary edema at 5 to 14 days must be treated with diuretic agents. Additional experiments to study the relative rejection injury to heart and lungs and the physiology of cardiopulmonary denervation are proposed.